A framework and mechanistically focused, in silico method for enabling rational translational research.

Abstract

A precondition for understanding if-and-when observations on wet-lab research models can translate to patients (and vice versa) is to have a method that enables anticipating how each system at the mechanism level will respond to the same or similar new intervention. A new class of mechanistic, in silico analogues is described. We argue that, although abstract, they enable developing that method. Building an analogue of each system within a common framework allows exploration of how one analogue might undergo (automated) metamorphosis to become the other. When successful, a concrete mapping is achieved. We hypothesize that such a mapping is, itself, an analogue of a corresponding mapping between the two referent systems. The analogue mapping can help establish how targeted aspects of the two referent systems are similar and different, at the mechanistic level and, importantly, at the systemic, emergent property level. The vision is that the analogues along with the metamorphosis method can be improved iteratively as part of a rational approach to translational research.